Larger Pore Size Hollow Fiber Membranes as a Solution to the Product Retention Issue in Filtration-Based Perfusion Bioreactors
Larger Pore Size Hollow Fiber Membranes as a Solution to the Product Retention Issue in Filtration-Based Perfusion Bioreactors
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DOI：
10.1002/biot.201800137
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发表时间：
2019-02-01
影响因子：
4.7
通讯作者：
Coffman, Jon
中科院分区：
文献类型：
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作者：
Wang, Samantha B.;Godfrey, Scott;Coffman, Jon
使用中空纤维膜的切向流过滤（TFF）和交替切向流（ATF）过滤技术通常用于灌注细胞培养以生产单克隆抗体；然而，产品保留仍然是这些系统的一个已知且常见的问题。为了解决这个问题，对标称孔径从几百道尔顿 (kDa) 到 0.65 μm 的市售中空纤维进行了测试，并证明它们都具有中度至重度的产品滞留能力。进一步的研究表明，颗粒的积累与孔隙的尺寸范围（大约 20-200 nm）相同。基于这些颗粒有助于产品截留和膜堵塞的假设，随后鉴定出具有非常规较大孔径的中空纤维，并证明其可以大幅降低产品截留而不影响细胞澄清。此外，这些中空纤维表现出令人惊讶的高膜容量，使其成为灌注反应器中产品保留问题的有吸引力的解决方案。
Tangential flow filtration (TFF) and alternating tangential flow (ATF) filtration technologies using hollow fiber membranes are commonly utilized in perfusion cell culture for the production of monoclonal antibodies; however, product retention remains a known and common problem with these systems. To address this issue, commercially available hollow fibers ranging from several hundred kilo-Daltons (kDa) to 0.65 mu m in nominal pore size are tested and are all demonstrated to undergo moderate to severe product retention. Further investigation revealed accumulation of particles in the same size range (approximate to 20-200 nm) as the pores. Based on the assumption that these particles contribute to product retention and membrane plugging, a hollow fiber with an unconventionally larger pore size is subsequently identified and demonstrated to drastically reduce product retention with no impact to cell clarification. Furthermore, these hollow fibers demonstrate surprisingly high membrane capacities, making them an attractive solution to the problem of product retention in perfusion reactors.